A variety of genetic anomalies result in craniofacial defects as a result of perturbations of normal patterns of development. In this project, we will characterize craniofacial problems associated with segmental trisomy 16 mice (Ts65Dn mice) which display dosage imbalance for many of the same genes present at extra copies in Down Syndrome. The increasingly powerful tools available for genetic analysis and animal model development provide an experimental approach to the identification of genes whose misexpression when present in three copies contributes to craniofacial anomalies. These animal models provide systematic access to all tissues at all stages of development. Localization of these genes is accomplished using YAC transgenic mice with dosage imbalance for subsets of Chr21 and the syntenic region of mouse Chr 16. The specific aims of the study are: 1) quantification of the craniofacial morphological differences between control and segmentally trisomy 16 mice at birth; 2) determination of the embryological timing of the first detectable morphological differences between normal and trisomic mice; and 3) assessment of the contribution to maldevelopment of specific genes or chromosome segments in transgenic and YAC transgenic mice.